Protein Deficiency Research Articles

The relationship between serum CTRP-5, C3a/desArg, and complement-C3 levels and hypothyroidism in women with polycystic ovary syndrome

IntroductionMany patients with polycystic ovary syndrome (PCOS) also experience thyroid disorders. There is a notable similarity in energy metabolism among PCOS, C1q/tumor necrosis factor (TNF)-related proteins (CTRP-5)deficiency, C3a/desArg (also known as acylation-stimulating protein (ASP)) deficiency, and hypothyroidism. This study aimed to investigate the relationship between serum levels of these factors and hypothyroidism in patients with PCOS. Improved clarity and vocabulary, corrected minor grammatical issues, and enhanced readability.MethodsThis case-control study involved three groups: healthy women (control group), women with PCOS and hypothyroidism, and women with PCOS without hypothyroidism. Serum levels of FBS, total cholesterol, triglycerides, and HDL-C were measured using enzymatic and colorimetric methods. TSH, T4, T3, and anti-thyroid peroxidase (Anti-TPO) levels were determined by ELISA to screen for hypothyroidism in women with PCOS. Additionally, serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), CTRP-5, ASP, and complement C3 were assessed using the ELISA method.ResultsThe results indicated that reduced blood levels of CTRP-5, along with elevated levels of ASP (C3a/desArg) and complement C3 in patients with PCOS, may be linked to dysregulation of the thyroid gland. Furthermore, the study observed that changes in these parameters, in conjunction with thyroid dysfunction, are associated with pathological alterations in lipid profiles and blood glucose levels.ConclusionWhile changes in CTRP-5, ASP, and complement C3 can influence energy expenditure and storage in PCOS and thyroid function, the complex nature of PCOS requires further research to investigate the prevalence of hypothyroidism in individuals with PCOS.Clinical trial numberNot applicable

Ultrastructural organization of the liver of rat pups in early postnatal ontogenesis when pregnant and lactating rats are kept on a low-protein diet

ABSTRACT Protein deficiency in the diet during pregnancy and lactation has a serious impact on the offspring by programming a predisposition to such serious diseases as hypertension and type 2 diabetes mellitus. In our study, we examined liver ultrastructure of rat pups at ages 2, 21, and 40 days with maternal protein deficiency. Body weight of the pups progressively lagged behind the control throughout the experiment, and the timing of eye opening indicated a slowdown of development. In the liver of 2-day-old animals, the proportion of hematopoietic cells at early stages of differentiation was higher as compared to the control. At the ultrastructural level, no obvious pathological changes were revealed, but a decrease in the amount of organelles was observed simultaneously with accumulation of lipids and glycogen. In the course of the experiment, a progressive decrease in the amount of the rough endoplasmic reticulum and ribosomes and increasing accumulation of glycogen in the cytoplasm of hepatocytes were noted. The most pronounced difference in ultrastructure between periportal and pericentral hepatocytes of control rat pups was detected on the 40th day of development, whereas in the low-protein diet group, the difference was weakly pronounced throughout the experiment. Thus, we showed that with prenatal and early postnatal protein deficiency, the growth and development of rat pups slows down, and glycogen accumulates excessively in the liver concurrently with a decrease in the amount of organelles.

Mitochondrial trifunctional protein deficiency caused by a deep intronic deletion leading to aberrant splicing

AbstractTrifunctional protein deficiency (TFP) is a disorder of fatty acid beta‐oxidation associated with metabolic, cardiac, and liver dysfunction in severe forms. We present two siblings diagnosed by newborn screening and confirmed by biochemical testing at birth. Their clinical course was complicated by recurrent rhabdomyolysis, retinopathy, and hypoparathyroidism. Both siblings were also diagnosed with focal segmental glomerulosclerosis (FSGS) and bone marrow failure and ultimately died of hypoxemic respiratory failure. Initial sequencing of the TFP‐associated genes HADHA and HADHB showed only a paternally inherited variant in HADHB, NM_000183.3:c.1059del (p.Gly354AspfsTer10). Subsequent evaluation by the Undiagnosed Diseases Network with genome and transcriptome sequencing revealed a rare maternally inherited 17 base pair deletion in HADHB, NM_000183.3:c.1390‐515_1390‐499del, located in the final intron and resulting in a pseudoexon that harbors a premature termination codon. Both sisters were compound heterozygous for this and the paternal premature termination codon. No other variants were detected that were potentially causative for the FSGS and bone marrow failure on genome sequencing. A review of the literature at that time revealed several case reports of the uncommon clinical findings of FSGS, bone marrow failure, and pulmonary involvement in patients with TFP, confirming this clinical diagnosis as the complete explanation for these siblings.

Effect of Fruit Load on Seed Quality of Cowpea Varieties [Vigna unguiculata (L.) Walp. (Fabaceae)

Background: The development of cowpea cultivation needs to be given priority because, in developing countries, cowpeas make up for many protein deficiencies. Producing quality seeds of this legume would be an essential objective if food security is to be achieved. This study aimed to establish the appropriate fruit load for optimum production of quality cowpea seed. Methods: To achieve this, the impact of five different fruit loads (10, 20, 30, 40 and 50 pods per plant) on the yield of four cowpea varieties (KVx745-11P (V1), KVx775-33-2G (Tiligré) (V2), Gourgou (V3) and KVx780-6 (V4)) was assessed. The seeds’ germination capacity and the seedlings’ vigor were then assessed for each of the four varieties. Result: Findings showed that seed length, width, thickness and weight changed significantly with increasing load in all varieties. The shortest time to emergence was recorded in the V1 variety for seeds from fruit loads of 20, 30, 40 and 50 pods per plant. For the ten pods per plant fruit load, the shortest emergence time was achieved with the V4 variety. The varieties V1, V2 and V4 studied produced excellent agronomic quality seeds when the pod was harvested with a load of 10 pods per plant. The fruit load significantly affected the seed quality and yield across all four varieties. Seeds from the minor C10 load for varieties V1, V2 and V4 and C20 for variety V3 exhibit high seedling vigour.

Rbm24-mediated post-transcriptional regulation of skeletal and cardiac muscle development, function and regeneration.

RNA-binding proteins are critically involved in the post-transcriptional control of gene expression during embryonic development and in adult life, contributing to regulating cell differentiation and maintaining tissue homeostasis. Compared to the relatively well documented functions of transcription factors, the regulatory roles of RNA-binding proteins in muscle development and function remain largely elusive. However, deficiency of many RNA-binding proteins has been associated with muscular defects, neuromuscular disorders and heart diseases, such as myotonic dystrophy, amyotrophic lateral sclerosis, and cardiomyopathy. Rbm24 is highly conserved among vertebrates and is one of the best characterized RNA-binding proteins with crucial implication in the myogenic and cardiomyogenic programs. It presents the distinctive particularity of displaying highly restricted expression in both skeletal and cardiac muscles, with changes in subcellular localization during the process of differentiation. Functional analyses using different vertebrate models have clearly demonstrated its requirement for skeletal muscle differentiation and regeneration as well as for myocardium organization and cardiac function, by regulating the expression of both common and distinct target genes in these tissues. The challenge remains to decipher the dynamic feature of post-transcriptional circuits regulated by Rbm24 during skeletal myogenesis, cardiomyogenesis, and muscle repair. This review discusses current understanding of its function in striated muscles and its possible implication in human disease, with the aim of identifying research gaps for future investigation.

Novel Therapies for Pancreatic Cancer.

Pancreatic adenocarcinoma (PDAC) unfortunately remains a highly fatal disease with a 5-year survival rate of only 11%. If surgical resection is not possible, systemic chemotherapy represents the standard-of-care approach to management. Combination chemotherapy regimens using fluorouracil (fluorouracil, oxaliplatin, leucovorin, and irinotecan; and fluorouracil, leucovorin, and oxaliplatin) or gemcitabine with albumin-bound paclitaxel have the potential to improve overall survival for patients with advanced disease. With the increasing understanding of the molecular drivers of pancreatic cancer, novel therapeutic approaches have made incremental progress for these patients. The molecular landscape of PDAC has been studied extensively. Approximately 90% of PDACs harbor mutations in the KRAS gene, a driver mutation that has long been considered undruggable. However, novel KRAS inhibitors have shown therapeutic promise in early-phase clinical trials, with larger studies ongoing. Less frequently encountered genomic aberrations that have therapeutic potential include NRG, BRAF, NTRK, HER2, BRCA, PALB2, and claudin. Immune checkpoint inhibitors have unfortunately yielded disappointing efficacy for the majority of patients with pancreatic cancer, except for those with tumors exhibiting deficiency in mismatch repair proteins. Alternative approaches to incorporate immunotherapy have shown more promise such as use of immune checkpoint inhibitors for selected patients in the maintenance setting and potential vaccine therapies in the postsurgery adjuvant setting. It is vital to perform molecular profiling in all patients with PDAC to identify potential treatment targets, and to enroll patients in clinical trials whenever possible.

Concomitant telomere attrition is associated with spinal muscular atrophy in highly inbred region of North India: unraveling the thread in Kashmir region

Spinal muscular atrophy (SMA) is a rare genetic disorder that unequivocally results in the degeneration of motor neurons, leading to muscle weakness and atrophy. This condition is caused by a mutation in the survival motor neuron 1 (SMN1) gene, which inevitably results in a deficiency of the SMN protein. In present study, we investigated the potential role of telomere attrition in SMA patients. Relative telomere length in peripheral blood lymphocytes was measured by Monochrome Multiplex Quantitative Polymerase Chain Reaction (MMQPCR) in 98 subjects and we conclusively found that SMA cases exhibit telomere attrition compared to healthy controls (P = 4 × 10− 2). Moreover, significant attrition was also observed in severe form of SMA, i.e. SMA type 0 (P = 0.04) as well.Although, the exact mechanism through which telomere shortening contributes to the pathogenesis of SMA is not fully understood and is yet to be delineated. However, one possibility is that telomere shortening leads to genomic instability and DNA damage, which can contribute to motor neuron degeneration. Another possibility is that telomere shortening leads to cellular senescence, which can impair the ability of motor neurons to regenerate and repair themselves. Recent studies have suggested that telomere shortening may be a potential therapeutic target in SMA. Thus, understanding the role of SMN1 gene in disease pathogenesis & its effect on telomere length will aid in estimating the risk & prognosis of SMA in genetically less explored & highly inbred region of Kashmir, Northern India.

Hippocampal exosomes from stroke aggravate post-stroke depression by regulating the expression of proBDNF and p75NTR and altering spine density

Post-stroke depression (PSD) affects millions of patients who suffer cerebral stroke. However, the molecular mechanisms and pathophysiology are poorly understood. Previous studies have shown that exosomes have been proven to be involved in neuropsychiatric disorders such as stroke and post-stroke depression in neurotransmitter release, neuronal remodeling, and neuron angiogenesis. Here we extracted and purified hippocampal exosomes from stroke mouse model to investigate mechanisms of hippocampal exocytosis in PSD assessed by using behavioral tests and biochemical methods. Aiming at the effect of hippocampal exosomes from stroke on the development of PSD, behavioral test was compared including sugar water preference experiment, open fields, forced swimming test, to explore it in depth. Further, the expression of depression-related protein (proBDNF and p75NTR) and synapse-associated proteins (Synaptotagmin and PSD95) was evaluated by Western blotting, RT-qPCR or immunofluorescence staining. Density of dendritic protrusions of neurons was assessed by Golgi staining to measure changes in spine density after the treatment of hippocampal exosomes from stroke. Our results revealed that injection of exosomes from stroke models significantly aggravated depressive-like behaviors, increase of depression-related protein (proBDNF and p75NTR) expression and deficiency of synapse-associated proteins (Synaptotagmin and PSD95) expression, and the decreased number of spin density. Our findings together suggest that hippocampal exosomes from stroke cause exacerbation of depressive-like behavior in mice, possibly resulting from the regulation of neurogenesis by its depression-associated proteins (proBDNF and p75NTR). Therefore, hippocampal exosomes from stroke are promising targets for the diagnosis and treatment of PSD.

Mainstreaming cancer genetics: feasibility of an advanced nurse practitioner-led service diagnosing Lynch syndrome from colorectal cancer in Ireland.

Colorectal cancer (CRC) is a common cancer in Ireland. Of all CRCs, 2-4% are attributable to Lynch Syndrome (LS), the most common CRC predisposition syndrome. LS is caused by constitutional pathogenic variants (PVs) affecting mismatch repair (MMR) genes with resultant MMR protein deficiency (dMMR). Screening of all CRCs with MMR immunohistochemistry (IHC) testing is advocated to increase the detection of LS. However, successful implementation requires appropriate downstream management. In Ireland the traditional pathway involves referral to cancer genetics services to assess eligibility for genetic testing. Cancer genetics services in Ireland face many challenges in providing uniform access to timely healthcare with current wait times for assessment in excess of 1 year. An increasingly adopted pathway is that of mainstreaming, whereby genetic testing is managed locally by a multidisciplinary team member. Our institution therefore implemented an Advanced Nurse Practitioner (ANP)-led service with responsibility for the LS Diagnostic Pathway and mainstream genetic testing. Data was extracted from a prospectively maintained database of all newly diagnosed CRC patients discussed at our institutions CRC multidisciplinary meeting (MDM) between January 1st, 2023, and May 31st, 2024. MMR IHC testing was performed in 97.9% of the 385 patients diagnosed with CRC. The median time from histological confirmation of CRC to the availability of the MMR IHC report was 6 days. All 51 patients (100%) who required sequential tumor testing underwent BRAF V600 ± MLH1 promoter methylation testing. Additionally, 100% of the 14 patients eligible for mainstream genetic testing were referred to the ANP-led genetics service. The median time from the initial MDM discussion to the initiation of genetic testing was 69 days, while the median time from testing to the availability of results was 19 days. Patients received their results within a median of 21 days. MMR IHC testing increases the detection of LS through identification of dMMR tumours. Successful downstream delivery of clinical services, however, requires appropriate subsequent management, in a resource-limited environment. Our institutional experience demonstrates the feasibility, efficiency, and effectiveness of an ANP-led mainstreaming model of care for hereditary colorectal cancer.

Genotype and grain pretreatment effects on digestibility of sorghum proteins in the Ethiopian fermented bread

AbstractBackground and ObjectivesSorghum is the principal food source for smallholder farmers in Sub‐Saharan Africa. Animal proteins are beyond economic reach, and only few food legumes are well‐adapted in major sorghum‐growing regions. Hence, sorghum serves as the primary source of protein and calories. However, the low digestibility of its proteins renders the communities vulnerable to protein malnutrition. Several factors, including genotypes and processing methods, have been shown to affect the digestibility of proteins in sorghum food products. The objective of this study was to investigate the impact of grain pretreatment on the protein digestibility of Ethiopian fermented flatbread.FindingsThe effect of four grain pretreatment processes: decortication, sprouting, parching, and untreated control was compared using four diverse sorghum genotypes milled to medium (2 mm) and fine (0.5 mm) particle sizes. The in‐vitro protein digestibility (IVPD) was significantly lower in the parched samples compared to the unprocessed control, while sprouting significantly increased IVPD. Decortication appears to have no impact on IVPD. Finer particle size tended to enhance IVPD in all genotypes and for all pretreatement methods. The treatments had no significant effect on protein content except the sprouting consistently but marginally increased total protein.ConclusionsSprouting sorghum grains can significantly improve the protein digestibility of fermented breads. Given that it involves little cost, the process can be readily adopted by the local community, provided that they are educated about the impact of protein deficiency on the health and productivity of the community.Significance and NoveltyLow‐cost grain pretreatment procedures such as sprouting can have a significant impact on the availability of nutrients, especially protein, the most limiting nutrient in smallholder communities. Combining the procedure with genetically enhanced varieties and improved cropping systems that integrate food legumes can significantly enhnace protein nutrition for smallholder farmers.

A Thrilling Case of Anemia

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare bone marrow failure disorder that presents with triad of peripheral blood cytopenias, hemolytic anemia and thrombosis. The absence of two glycosylphosphatidylinositol (GPI)-anchored proteins, CD55 and CD59, leads to uncontrolled complement activation that accounts for hemolysis and other PNH manifestations. GPI anchor protein deficiency is due to acquired somatic mutations in phosphatidylinositol glycan class A (PIGA) gene.Terminal complement inhibition with eculizumab and allogeneic bone marrow transplantation (BMT) are the only widely effective therapies for patients with classical PNH. Compared to eculizumab and ravulizumab that block the fifth component of complement (C5), pegcetacoplan blocks the third component of complement (C3).

DNAH3 deficiency causes flagellar inner dynein arm loss and male infertility in humans and mice

Axonemal protein complexes, including the outer and inner dynein arms (ODA/IDA), are highly ordered structures of the sperm flagella that drive sperm motility. Deficiencies in several axonemal proteins have been associated with male infertility, which is characterized by asthenozoospermia or asthenoteratozoospermia. Dynein axonemal heavy chain 3 (DNAH3) resides in the IDA and is highly expressed in the testis. However, the relationship between DNAH3 and male infertility is still unclear. Herein, we identified biallelic variants of DNAH3 in four unrelated Han Chinese infertile men with asthenoteratozoospermia through whole-exome sequencing (WES). These variants contributed to deficient DNAH3 expression in the patients’ sperm flagella. Importantly, the patients represented the anomalous sperm flagellar morphology, and the flagellar ultrastructure was severely disrupted. Intriguingly, Dnah3 knockout (KO) male mice were also infertile, especially showing the severe reduction in sperm movement with the abnormal IDA and mitochondrion structure. Mechanically, nonfunctional DNAH3 expression resulted in decreased expression of IDA-associated proteins in the spermatozoa flagella of patients and KO mice, including DNAH1, DNAH6, and DNALI1, the deletion of which has been involved in disruption of sperm motility. Moreover, the infertility of patients with DNAH3 variants and Dnah3 KO mice could be rescued by intracytoplasmic sperm injection (ICSI) treatment. Our findings indicated that DNAH3 is a novel pathogenic gene for asthenoteratozoospermia and may further contribute to the diagnosis, genetic counseling, and prognosis of male infertility.

DNAH3 deficiency causes flagellar inner dynein arm loss and male infertility in humans and mice.

Axonemal protein complexes, including the outer and inner dynein arms (ODA/IDA), are highly ordered structures of the sperm flagella that drive sperm motility. Deficiencies in several axonemal proteins have been associated with male infertility, which is characterized by asthenozoospermia or asthenoteratozoospermia. Dynein axonemal heavy chain 3 (DNAH3) resides in the IDA and is highly expressed in the testis. However, the relationship between DNAH3 and male infertility is still unclear. Herein, we identified biallelic variants of DNAH3 in four unrelated Han Chinese infertile men with asthenoteratozoospermia through whole-exome sequencing (WES). These variants contributed to deficient DNAH3 expression in the patients' sperm flagella. Importantly, the patients represented the anomalous sperm flagellar morphology, and the flagellar ultrastructure was severely disrupted. Intriguingly, Dnah3 knockout (KO) male mice were also infertile, especially showing the severe reduction in sperm movement with the abnormal IDA and mitochondrion structure. Mechanically, nonfunctional DNAH3 expression resulted in decreased expression of IDA-associated proteins in the spermatozoa flagella of patients and KO mice, including DNAH1, DNAH6, and DNALI1, the deletion of which has been involved in disruption of sperm motility. Moreover, the infertility of patients with DNAH3 variants and Dnah3 KO mice could be rescued by intracytoplasmic sperm injection (ICSI) treatment. Our findings indicated that DNAH3 is a novel pathogenic gene for asthenoteratozoospermia and may further contribute to the diagnosis, genetic counseling, and prognosis of male infertility.

Giardia antagonizes beneficial functions of indigenous and therapeutic intestinal bacteria during protein deficiency

ABSTRACT Undernutrition in children commonly disrupts the structure and function of the small intestinal microbial community, leading to enteropathies, compromised metabolic health, and impaired growth and development. The mechanisms by which diet and microbes mediate the balance between commensal and pathogenic intestinal flora remain elusive. In a murine model of undernutrition, we investigated the direct interactions Giardia lamblia, a prevalent small intestinal pathogen, on indigenous microbiota and specifically on Lactobacillus strains known for their mucosal and growth homeostatic properties. Our research reveals that Giardia colonization shifts the balance of lactic acid bacteria, causing a relative decrease in Lactobacillus spp. and an increase in Bifidobacterium spp. This alteration corresponds with a decrease in multiple indicators of mucosal and nutritional homeostasis. Additionally, protein-deficient conditions coupled with Giardia infection exacerbate the rise of primary bile acids and susceptibility to bile acid-induced intestinal barrier damage. In epithelial cell monolayers, Lactobacillus spp. mitigated bile acid-induced permeability, showing strain-dependent protective effects. In vivo, L. plantarum, either alone or within a Lactobacillus spp consortium, facilitated growth in protein-deficient mice, an effect attenuated by Giardia, despite not inhibiting Lactobacillus colonization. These results highlight Giardia’s potential role as a disruptor of probiotic functional activity, underscoring the imperative for further research into the complex interactions between parasites and bacteria under conditions of nutritional deficiency.

Investigation of the Relationship Between DNA Mismatch Repair Genes and Microsatellite Instability in Solid Tumors

Aim: In this study, we aimed to detect the MSI status and somatic mutations in MMR genes (MSH2, MSH6, MLH1, PMS2) of a total of 55 solid tumors diagnosed with colorectal, endometrium and ovarian cancer by NGS method and to reveal the relationship between them. Material and Method: DNA isolation was performed by taking 10-micron sections from paraffin-embedded tissue samples of 55 patients diagnosed with kolorektal, endometrium ve ovarian solid tümörlerinin and Kapa NGS DNA extraction kit was used for sequence analysis. The purity and concentration of the DNA obtained was measured by Qubit fluoremeter, and NadPrep DNA Universal Library Preparation Kit was used for high quality library preparation. Bioinformatics analyses were performed on the Genomize Seq platform. The MSI value was analysed by Roche Navify Mutation Caller software and percentage MSI values were determined using the MSIsensor2 pipeline for secondary analysis of NGS. Results: All ovarian tumors were in the MSI-Stable category. The average MSI value was 2.01. One sample had an MSI of zero. In addition, no mutations in the MSH2 and MLH1 genes were detected in any of the ovarian tumors. 3 of 4 endometrial tumors were in the MSI-Stable category, and 1 tumor was in the MSI-low (MSI value: 13.2) category. No variants were detected in the MSH2 and PMS2 genes in endometrial tumors. 2 of the 41 colorectal tumors (Case4, Case16) were in the MSI-High category. No variants were detected in the MMR genes in 19 tumors. Conclusion: Although frame-shift and stop-gain mutations were detected in 23 tumors that would cause protein deficiency in MMR genes, MSI-H was not detected, as expected, except for two colorectal tumors. Therefore, the results of our study emphasise the need to define new predictive biomarkers clinically within the framework of algorithms to predict response to immunotherapy and determine prognosis.

Massage Therapy In One Year Old Babies with Increased Appetie

Massage often referred to as tactile stimulation, is a long-practiced art of health care and medicine. Baby massage can enhance the release of digestive hormones such as insulin and gastrin, leading to improved food absorption. This may result in the baby feeling hungry more frequently, potentially contributing to weight gain. Prolonged eating difficulties in children can lead to disrupted nutritional intake, including deficiencies in calories, protein, vitamins, minerals, electrolytes, and anemia. The study used a retrospective data analysis design with a chi-square test, involving a sample of 20 babies who received 12 massage sessions at Momby Kids Jombang. The total sampling method was employed. The findings revealed a significance value of 0.003, indicating a statistically significant relationship between baby massage and increased appetite. The study concluded that baby massage is indeed linked to an increase in appetite in babies.

Blood biochemical parameters of rats fed with powder from the flesh of the Limicolaria flammea snail

With a view to the nutritional value of the Limicolaria flamea snail and the contribution to the fight against protein deficiencies, our study consisted of determining the blood biochemical parameters, blood mineral levels and serum enzyme activity in rats fed the different diets (ESC, RTC and RPP), in particular the diet containing powder derived from the flesh of the Limicolaria flammea snail. After the rats had been fed the diets on a daily basis for 15 days, the protein intake of the diets was used to measure the effect of consuming powder derived from the flesh of the Limicolaria flammea snail on the biochemical and mineral indicators of the rats fed the different diets. The results show that the urea content of rats fed the RTC, ESC and RPP diets respectively was 0.26 ± 0.06 g/L, 0.3 ± 0.15 g/L and 0.29 ± 0.01 respectively. The creatinine values in the blood of rats on their respective diets (RTC, ESC and RPP) were 3.25 ± 0.5 g/L, 3.25 ± 0.5 g/L and 3.5 ± 0.57 g/L respectively. Thus, the serum enzyme values of the rats on their respective diets showed no significant difference at the 5 % threshold, particularly for serum enzymes such as Aspartane Amino Transferase (ASAT) and Alanine Amino Transferase (ALAT).

GPRASP protein deficiency triggers lymphoproliferative disease by affecting B-cell differentiation.

Gprasp1 and Gprasp2 encode proteins that control the stability and cellular trafficking of CXCR4, a master regulator of hematopoiesis whose dynamic regulation is required for appropriate trafficking of B-cells in the germinal center (GC). Here, we report that Gprasp1 and Gprasp2-deficient B-cells accumulate in the GC and show transcriptional abnormalities, affecting the mechanisms controlling Aicda expression and exposing them to excessive somatic hypermutation. Consequently, about 30% of mice transplanted with Gprasp-deficient hematopoietic stem and progenitor cells developed a biologically aggressive and fatal B-cell hyperproliferative disease by 20-50 weeks posttransplant. Histological and molecular profiling reveal that Gprasp1- and Gprasp2-deficient neoplasms morphologically resemble human high-grade B-cell lymphomas of germinal center origin with shared morphologic features of both Burkitt Lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), and molecular features consistent with DLBCL, as well as elevated mutational burden and heterogenous transcriptional and mutational signature. Thus, reduced Gprasp1 and Gprasp2 gene expression perturbs B-cell maturation and increases the risk of B-cell neoplasms of germinal center origin. As this model recapitulates the essential features of the heterogenous group of human hematopoietic malignancies, it could be a powerful tool to interrogate the mechanisms of lymphomagenesis for these cancers.

Biochemical characterization of sesame (Sesamum indicum L.) varieties grown in Togo

Food and nutrition insecurity are a major problem in low-income countries. However, some crops like sesame are still underused and can be used to improve the food and nutritional security in rural areas. Grains of seven varieties of sesame comprising four (4) local and three (3) introduced varieties were studied for their nutrient content and oil composition to provide information on their nutritional value and oil quality for a holistic development and valorisation of the crop in Togo. Results revealed that water, ash, lipid, protein, total sugar, fiber, vitamin C, energy, total phenol and tannin contents ranged from 5.08 % to 6.30 %; 3.94–5.40 %; 36.69–45.62 %; 19.52–25.37; 11.10–19.16; 3.84–7.01 %; 1.10–1.94 %; 660–953.3 Kcal/ 100 g; 0.0020–7–0.006 % and 0.005–0.017 %. The oils extracted from these different varieties had saponification and acid indices that ranged respectively from 179.95 to 190.54 and from 4.47 to 8.96. In terms of fatty acid composition, oleic acid and linoleic acid ranged from 37.92 % to 42.24 % and 36.1–39.8 % respectively, while palmitic acid ranged from 6.82 % to 12.41 % and stearic acid from 5.51 % to 7.83 %. The results enabled us to identify the sesame grains of local varieties G3 and G3B as being suitable for enriching infant flours or for remedying the problems of protein and energy deficiency in Togo. Further, the oils extracted from these varieties are of good quality and can therefore be used in industry and for food purposes.

Overview on Hereditary Spherocytosis Diagnosis.

Hereditary spherocytosis (HS) is a congenital haemolytic disorder, resulting from plasma membrane protein deficiency of red blood cells (RBCs). Typical pathological signs are anemia, jaundice, and splenomegaly; in newborns, jaundice is the main symptom. This study focused on the state of art about the HS diagnosis, from traditional to innovative methods, including diagnostic algorithms that can be applied for pediatric and adult patients, for different laboratory diagnostic levels. The first erythrocyte parameters used for HS diagnosis were the mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), and red blood cell distribution width (RDW); nowadays new parameters are used in blood cell counter. Advia analyzers (Siemens Medical Solutions) supply the hyper-dense cell percentage (% Hyper), which reflects the red blood cells hyperchromia. Sysmex instruments (i.e. XT-4000i, XE-5000, XN-Series) provide the MicroR, that is the percentage of erythrocytes smaller than 60 fL, Hypo-He, which is the percentage of erythrocytes with a content of hemoglobin less than 17 pg and % Hyper-He, which represents the percentage of RBC with cellular hemoglobin content higher than 49 pg. CELL-DYN Sapphire (Abbott Diagnostics) introduced the HPR parameter (% HPR), which represents the erythrocytes with hemoglobin > 410 g/L. Beckman Coulter instruments supply the mean sphered corpuscular volume (MSCV), which is the average volume of all erythrocytes, including mature erythrocytes and reticulocytes. Other reference tests for screening and diagnosis of HS are the acidified glycerol lysis test (AGLT), the eosin-5-maleimide (EMA) binding test and genetic testing by next-generation sequencing. The diagnostic workup of hereditary spherocytosis could be improved thanks to all the available tests, including new molecular tools. However, it requires synergy between clinicians and laboratory staff, evaluating clinical manifestations, all available data related to the disease and the prognosis to fill the diagnostic gaps in the near future.