ERK1/2 pro-survival signalling is suppressed by pirtobrutinib in ibrutinib-resistant MYD88-mutated lymphoma cells.

Covalent Bruton's tyrosine kinase-inhibitors (cBTK-i) are highly active in MYD88-mutated (MYD88Mut) Waldenstrom's macroglobulinaemia and suppress nuclear factor kappa-light-chain-enhancer of activated B cells and extracellular signal-regulated kinases-1/2 (ERK1/2)-related signalling. BTKCys481 mutations are associated with cBTK-i acquired resistance and are accompanied by reactivation of ERK1/2 that promotes inflammatory cytokine secretion and paracrine-mediated resistance of BTK wild-type (BTKWT) tumour cells. Pirtobrutinib is a non-covalent BTK-inhibitor that binds at non-BTKCys481 sites. We show that pirtobrutinib blocked p-ERK1/2, ERK1/2-driven inflammatory cytokines, and overcame paracrine-mediated resistance in MYD88Mut lymphoma cells expressing mutated BTKCys481. Our results provide important mechanistic insights for the activity of pirtobrutinib in MYD88Mut lymphomas carrying BTKCys481 mutations.

Structural, optical, magnetic, and enhanced antibacterial properties of hydrothermally synthesized Sm-incorporating α-MoO3 2D-layered nanoplates.

In this study, we have synthesized pristine and [0.5,1.5, and 2.5] M% samarium (Sm)-incorporating α-MoO3 2D-layered nanoplates utilizing a facile hydrothermal process, and investigated the physical properties along with antibacterial effectiveness. X-ray diffraction (XRD) patterns confirmed the single-phase, stable orthorhombic polycrystalline structure of the as-prepared samples. The crystallite size, lattice strain, and dislocation density were measured using both Debye-Scherrer (D-S) and Williamson-Hall (W-H) techniques. Both pristine and Sm-incorporating α-MoO3 samples showed two-dimensional (2D) layered nanoplate-type surface morphology, revealed by field emission scanning electron microscopy (FE-SEM) images. Energy dispersive X-ray spectroscopy (EDS) confirmed the presence of Sm contents in the α-MoO3 matrix. After Sm incorporation in α-MoO3, the different functional groups as well as vibrational groups were observed by Fourier-transform infrared (FTIR) spectroscopy and Raman spectroscopy analyses, respectively. The optical band gaps were measured from UV-vis diffuse reflectance spectroscopy (DRS) by employing the Kubelka-Munk formula and interestingly it is found that the bandgap energy (E g) gradually decreased from 2.96 to 2.83 eV with the increment of Sm content. When compared to pristine α-MoO3, the Sm-incorporating samples experienced a steady improvement in room temperature ferromagnetic (RTFM) behavior as Sm content increased, as measured by hysteresis loops. The antibacterial activities of both samples were assessed against Gram-positive: Staphylococcus aureus (S. aureus), and Gram-negative: Escherichia coli (E. coli) and Salmonella enteritidis (S. enteritidis) bacteria by the agar well diffusion method and enhanced antibacterial activity was observed as the Sm concentration increased, compared to pristine nanoplates. The obtained results suggest that the synthesized Sm-incorporating α-MoO3 2D-layered nanoplate could be a potential antibacterial agent.

Impact of gamma radiation, potassium sorbate and low temperature on shrimp (Penaeus monodon) preservation.

The objective this study was to assess the effect of gamma radiation and 2% potassium sorbate with low temperature (4 °C) for shrimp (Penaeus monodon) preservation. Fresh samples were prepared for treatment with gamma radiation at 1.0 and 1.5 kGy doses and potassium sorbate (2%) soaked for 30 s (PS 30 s) and 60 s (PS 60 s). Organoleptic score (OS), biochemical composition and microbiological analysis were performed to evaluate the shelf-life extension and quality changes during the storage periods. Data showed that combination treatment of gamma irradiation at 1.5 kGy with low temperature was the most effective in extending shelf-life of shrimp. The isolated bacteria associated with shrimp samples were identified through PCR technique. Antibiotic sensitivity test was examined using ten commonly used antibiotics against these pathogenic isolates. Gentamicin and Imipenem showed up to 50% resistance on Gram-positive (Bacillus cereus and Staphylococcus aureus). This study indicates that gamma irradiation treatment with low temperature was most effective way for shelf-life extension of shrimp which might reduce the wastage of this important nutritional source.

Detection of species adulteration in meat products and Mozzarella-type cheeses using duplex PCR of mitochondrial cyt b gene: A food safety concern in Bangladesh.

Food origin authentication is imperative for consumer protection. This study explored meat and milk species identification as a pioneering country-specific report on mislabeling prevalence among processed meat and milk products in Bangladesh. Meat products (64; sausages, burger patty, meatball, kabab) labeled as chicken or beef and Mozzarella-type cheeses (25), made in Bangladesh and of overseas origins, were analyzed for species detection. Two duplex PCR (cattle-buffalo and chicken-pig) were applied with species-specific mitochondrial Cyt b gene primers and determine to be accurate for species identification in meat and milk. Bangladeshi origin beef-labeled products were found to be mixed with buffalo (n = 2) and chicken (n = 5) suggesting up to one third of products might be mislabeled. Such mislabeling would allow these 'beef' products to charge a higher price compared with chicken products that command a lower price. Imported meat products were also found mislabeled with buffalo and chicken. Cheese samples, declared as bovine, were found to contain buffalo DNA, and no cattle or buffalo DNA was found in six imported cheese samples. All the meat and cheese products were Halal, as none contained pig DNA. This pilot study shows the majority of products were labelled correctly, but large proportions were not and strict monitoring is recommended to ensure food safety and address consumer preferences, especially religious concerns.

Role of fractal analysis in detection of dysplasia in potentially malignant disorders.

BACKGROUND: Fractal analysis is, a noninvasive method, used to determine the intricate characteristics of the matter. Oral leukoplakia (OL), a potential malignant disorder, has definite propensity to turn in to malignancy. In such lesions, fractal dimension analysis (FDA) could be helpful in the early detection of malignant transformation. OBJECTIVES: To determine the efficacy of fractal dimension analysis in detecting malignancy potential of oral leukoplakia. MATERIALS AND METHODS: After ethical clearance, we enrolled 121 patients in our study. Lesions were photographed before and after toluidine staining. Image J software was used to analyze fractal dimensions (FDs) of digital image and results were compared with biopsy. RESULTS: Fractal dimension value is significantly higher in leukoplakia with dysplastic changes. FD values increase as age of patients increases. FD value in leukoplakia with different tobacco products showed more positive correlation with surti/khaini abusers. CONCLUSION: Fractal dimension analysis is a useful method in determination of complication in OL cases and can be used as an effective, noninvasive screening tool at primary healthcare centers for early intervention.

Evidence-based diabetes care for older people with Type 2 diabetes: a critical review.

In our ageing society diabetes imposes a significant burden in terms of the numbers of people with the condition, diabetes-related complications including disability, and health and social care expenditure. Older people with diabetes can represent some of the more complex and difficult challenges facing the clinician working in different settings, and the recognition that we have only a relatively small (but increasing) evidence base to guide us in diabetes management is a limitation of our current approaches. Nevertheless, in this review we attempt to explore what evidence there is to guide us in a comprehensive scheme of treatment for older adults, often in a high-risk clinical state, in terms of glucose lowering, blood pressure and lipid management, frailty care and lifestyle interventions. We strive towards individualized care and make a call for action for more high-quality research using different trial designs.

Comparative study on alveolar bone healing in postextraction socket versus healing aided with autologous platelet-rich fibrin following surgical removal of bilateral mandibular impacted third molar tooth: A radiographic evaluation.

AIM: This study was to evaluate and compare the bone regeneration potential of autologous platelet-rich fibrin (PRF) placed in one of the extracted sockets after the surgical removal of bilateral impacted mandibular third molars. PATIENTS AND METHODS: Twenty-five patients (10 females and 15 males; 18-35 years old) were taken for surgical removal of bilateral impacted mandibular third molar, performed in the same session. The autologous PRF was placed in one of the extracted sockets whereas the opposite side was taken as control side, and primary closure was done. Radiographic examination with orthopantomogram was done preoperatively and 1 month, 3 months, and 6 months postoperatively to assess the degree of bone regeneration at the extracted site and compare it with the control side using MATLAB software and the data are statistically analyzed using paired t-test. RESULTS: PRF side had better healing and bone formation when compared with the control side as indicated by significant P values of (P = 0.06>5%) 1 month, (P = 0.00<1%) 3 month, and (P = 0.00<1%) 6 month postoperatively. The repeated-measures ANOVA showed a significant difference seen on 1st, 3rd, and 6th months postoperatively on PRF side (P = 0.001). CONCLUSION: The autologous PRF improves and fastens the bone regeneration and healing in the extracted sockets.

Early Results of Extreme Hypofractionation Using Stereotactic Body Radiation Therapy for High-risk, Very High-risk and Node-positive Prostate Cancer.

AIMS: Stereotactic body radiotherapy (SBRT) in low- and intermediate-risk prostate cancer has shown encouraging results. However, its use in high-risk patients is limited due to lack of data regarding adequate radiotherapy dose, need for pelvic nodal treatment and androgen deprivation therapy. Herein we report our experience of SBRT in this subgroup. MATERIALS AND METHODS: Analysis of a prospectively maintained database of 68 consecutive patients of the National Comprehensive Cancer Network (NCCN) high-risk, very high-risk and node-positive adenocarcinoma prostate treated with SBRT was undertaken. All patients were treated with rotational intensity-modulated radiotherapy with daily image guidance. The dose delivered to the prostate and gross node was 35-37.5 Gy in 5 alternate day fractions. Node-positive patients received 25 Gy to pelvic nodal regions until the common iliac nodes. Treatment was delivered in 7-10 days. All patients received long-term androgen deprivation therapy (79% medical and 21% surgical). RESULTS: Most patients (65%) had a Gleason score ≥ 8. The median prostate-specific antigen was 42. Twenty patients were high risk (30%), 11 (16%) very high risk and 37 (54%) node positive. No acute Radiation Therapy Oncology Group grade ≥ 3 genitourinary or gastrointestinal toxicity was noted. Acute grade 2 genitourinary and gastrointestinal toxicity were 12% and 3%, respectively. Late grade 3 genitourinary and gastrointestinal toxicity was 3% and 0%, respectively. There was no increase in acute or late gastrointestinal toxicity with prophylactic pelvic nodal radiotherapy. Prior transurethral resection of prostate (n = 11) did not increase toxicity. At a median follow-up of 18 months, 97% patients were alive and 94% were biochemically controlled. CONCLUSION: SBRT is safe in the treatment of high-risk, very high-risk and node-positive prostate cancer, even with prophylactic pelvic radiotherapy or prior transurethral resection of prostate. Longer follow-up is required to determine efficacy.

An International Position Statement on the Management of Frailty in Diabetes Mellitus: Summary of Recommendations 2017.

AIM: The International Position Statement provides the opportunity to summarise all existing clinical trial and best practice evidence for older people with frailty and diabetes. It is the first document of its kind and is intended to support clinical decisions that will enhance safety in management and promote high quality care. METHODS: The Review Group sought evidence from a wide range of studies that provide sufficient confidence (in the absence of grading) for the basis of each recommendation. This was supported by a given rationale and key references for our recommendations in each section, all of which have been reviewed by leading international experts. Searches for any relevant clinical evidence were generally limited to English language citations over the previous 15 years. The following databases were examined: Embase, Medline/PubMed, Cochrane Trials Register, Cinahl, and Science Citation. Hand searching of 16 key major peer-reviewed journals was undertaken by two reviewers (AJS and AA) and these included Lancet, Diabetes, Diabetologia, Diabetes Care, British Medical Journal, New England Journal of Medicine, Journal of the American Medical Association, Journal of Frailty and Aging, Journal of the American Medical Directors Association, and Journals of Gerontology - Series A Biological Sciences and Medical Sciences. RESULTS: Two scientific supporting statements have been provided that relate to the area of frailty and diabetes; this is accompanied by evidence-based decisions in 9 clinical domains. The Summary has been supported by diagrammatic figures and a table relating to the inter-relations between frailty and diabetes, a frailty assessment pathway, an exercise-based programme of intervention, a glucose-lowering algorithm with a description of available therapies. CONCLUSIONS: We have provided an up to date evidence-based approach to practical decision-making for older adults with frailty and diabetes. This Summary document includes a user-friendly set of recommendations that should be considered for implementation in primary, community-based and secondary care settings.

IRMPD Action Spectroscopy, ER-CID Experiments, and Theoretical Studies of Sodium Cationized Thymidine and 5-Methyluridine: Kinetic Trapping During the ESI Desolvation Process Preserves the Solution Structure of [Thd+Na].

Thymidine (dThd) is a fundamental building block of DNA nucleic acids, whereas 5-methyluridine (Thd) is a common modified nucleoside found in tRNA. In order to determine the conformations of the sodium cationized thymine nucleosides [dThd+Na]+ and [Thd+Na]+ produced by electrospray ionization, their infrared multiple photon dissociation (IRMPD) action spectra are measured. Complementary electronic structure calculations are performed to determine the stable low-energy conformations of these complexes. Geometry optimizations and frequency analyses are performed at the B3LYP/6-311+G(d,p) level of theory, whereas energies are calculated at the B3LYP/6-311+G(2d,2p) level of theory. As protonation preferentially stabilizes minor tautomers of dThd and Thd, tautomerization facilitated by Na+ binding is also considered. Comparisons of the measured IRMPD and computed IR spectra find that [dThd+Na]+ prefers tridentate (O2,O4',O5') coordination to the canonical 2,4-diketo form of dThd with thymine in a syn orientation. In contrast, [Thd+Na]+ prefers bidentate (O2,O2') coordination to the canonical 2,4-diketo tautomer of Thd with thymine in an anti orientation. Although 2,4-dihydroxy tautomers and O2 protonated thymine nucleosides coexist in the gas phase, no evidence for minor tautomers is observed for the sodium cationized species. Consistent with experimental observations, the computational results confirm that the sodium cationized thymine nucleosides exhibit a strong preference for the canonical form of the thymine nucleobase. Survival yield analyses based on energy-resolved collision-induced dissociation (ER-CID) experiments suggest that the relative stabilities of protonated and sodium cationized dThd and Thd follow the order [dThd+H]+ < [Thd+H]+ < [dThd+Na]+ < [Thd+Na]+. Graphical Abstract ᅟ.

Effects of sodium cationization versus protonation on the conformations and N-glycosidic bond stabilities of sodium cationized Urd and dUrd: solution conformation of [Urd+Na]+ is preserved upon ESI.

Uridine (Urd) is one of the naturally occurring pyrimidine nucleosides of RNA. 2'-Deoxyuridine (dUrd) is a naturally occurring modified form of Urd, but is not one of the canonical DNA nucleosides. In order to understand the effects of sodium cationization on the conformations and energetics of Urd and dUrd, infrared multiple photon dissociation (IRMPD) action spectroscopy experiments and density functional theory (DFT) calculations are performed. By comparing the calculated IR spectra of [Urd+Na]+ and [dUrd+Na]+ with the measured IRMPD spectra, the stable low-energy conformers populated in the experiments are determined. Anti oriented bidentate O2 and O2' binding conformers of [Urd+Na]+ are the dominant conformers populated in the experiments, whereas syn oriented tridentate O2, O4', and O5' binding conformers of [dUrd+Na]+ are dominantly populated in the experiments. The 2'-hydroxyl substituent of Urd stabilizes the anti oriented O2 binding conformers of [Urd+Na]+. Significant differences between the measured IRMPD and calculated IR spectra for complexes of [Urd+Na]+ and [dUrd+Na]+ involving minor tautomeric forms of the nucleobase make it obvious that none are populated in the experiments. Survival yield analyses based on energy-resolved collision-induced dissociation (ER-CID) experiments suggest that the relative stabilities of protonated and sodium cationized Urd and dUrd follow the order: [dUrd+H]+ < [Urd+H]+ < [dUrd+Na]+ < [Urd+Na]+. The 2'-deoxy modification is found to weaken the glycosidic bond of dUrd versus that of Urd for the sodium cationized uridine nucleosides.

Shortfalls of the use of HbA1C-derived eAG in older adults with diabetes.

AIMS: The hemoglobin HbA1C (HbA1C) value, translated into estimated average glucose concentration (eAG), is commonly used to assess glycaemic control and manage treatment regimens in people with diabetes. However, the relationships among HbA1C-derived eAG, and mean glucose concentration derived from continuous glucose monitoring (CGM) in different populations have not been well studied. We examined this relationship in older people with diabetes and compared the results to those currently used in clinical practice. METHODS: Data from three studies evaluating CGM in older adults (≥70 years of age), with stable glycaemic control were analyzed retrospectively. Mean glucose and mean amplitude of glucose excursion (MAGE) were calculated from CGM data and correlated with HbA1C and HbA1C-derived eAG using the ADAG study formula. RESULTS: HbA1C and CGM data were analyzed from 90 patients with mean age 76±5 years, HbA1C 7.9±1.2% (63±13 mmol/mol) and 77% with Type 2 diabetes. The HbA1C and HbA1C-derived eAG correlated significantly with CGM-measured mean glucose (r(2)=0.30, p<0.0001) and MAGE (r(2)=0.16, p=0.00013) in this population and all its subgroups, but the slopes of the relationship between HbA1C and eAG or CGM-measured mean glucose were significantly different. CONCLUSIONS: HbA1C-derived eAG values may not accurately reflect CGM-measured mean glucose or MAGE in older adults with diabetes. Wide glucose excursions should be considered and HbA1C should be interpreted cautiously when making treatment changes based on HbA1C.

Comparative Study of Raw and Boiled Silver Pomfret Fish from Coastal Area and Retail Market in Relation to Trace Metals and Proximate Composition.

Trace metals concentration and proximate composition of raw and boiled silver pomfret (Pampus argenteus) from coastal area and retail market were determined to gain the knowledge of the risk and benefits associated with indiscriminate consumption of marine fishes. The effects of cooking (boiling) on trace metal and proximate composition of silver pomfret fish were also investigated. Trace element results were determined by the Energy Dispersive X-ray Fluorescence (EDXRF) Spectrometer wherein fish samples from both areas exceeded the standard limits set by FAO/WHO for manganese, lead, cadmiumm and chromium and boiling has no significant effects on these three metal concentrations. Long-term intake of these contaminated fish samples can pose a health risk to humans who consume them.

The management of cubitus varus using Ilizarov method.

Cubitus varus is the most common complications of supracondylar fractures. Various combinations of osteotomy and fixation have been described to correct the deformity but each is associated with significant complications. In this study, we used distraction osteogenesis and Ilizarov frame fixation to treat 12 elbows with cubitus varus. The mean time to follow up was 24 months (10-38) and the mean time to frame removed was 14.5 weeks (10-22). The mean carrying angle was corrected from -19.8°(-10°-32°) to 6.2°(2°-12°). In patients with cubitus varus was from 35.5° (22°-45°). There were 11 excellent and one good result.

Which aspects of executive dysfunction influence ability to manage diabetes in older adults?

AIMS: To examine whether different aspects of executive function as measured by different assessment tools are associated with glycaemic control and other clinical characteristics in older adults with Type 2 diabetes. METHODS: We performed a cross-sectional study of older adults aged ≥ 70 years with Type 2 diabetes at a tertiary care diabetes centre. The Dysexecutive Questionnaire was used to measure self-reported executive dysfunction. Objective tests of executive functions included a modified clock drawing test (Clock-in-a-Box), Trail Making Tests (parts A and B) and verbal fluency. Demographic and clinical information was collected using questionnaires and surveys. Glycaemic control was measured by HbA(1c). RESULTS: We evaluated 145 patients [average age 77 ± 5 years, diabetes duration 15 ± 11 years, mean HbA(1c) 56 ± 11 mmol/mol (7.3 ± 1.1%)]. Poor performances on objective tests (low scores on Clock-in-a-Box and verbal fluency; and high scores on Trail Making Tests A and B) but not on the subjective test (the Dysexecutive Questionnaire), were associated with poor glycaemic control (r = -0.23, P < 0.005; r = -0.17, P < 0.04; r = 0.20, P < 0.01, r = 0.22, P < 0.008, r = -0.07, P < 0.42, respectively). In a multiple regression model (r(2) = 0.39), high Dysexecutive Questionnaire scores were associated with higher diabetes-related distress (P < 0.0004), depressive symptoms (P < 0.004), number of falls (P < 0.009), fear of falling (P < 0.01), less years of education (P < 0.0007) and fewer medications (P < 0.001). CONCLUSIONS: On the one hand, in older adults, executive dysfunction detected by objective tests is associated with poor glycaemic control and may be considered before prescribing complex treatment regimens. On the other hand, self-reported executive dysfunction is associated with risk and fear of falls, and more affective symptoms, which may indicate higher awareness of subtle deficits.

The role of the renin-angiotensin system in liver fibrosis.

Hepatic fibrosis, which is characterized by progressive inflammation and deposition of extracellular matrix components, is a common response to chronic liver disease. Hepatic fibrogenesis is a dynamic process that involves several liver cell types including hepatic stellate cells and Kupffer cells. In addition, recent evidence indicates that bile duct epithelial cells (i.e. cholangiocytes) also participate in the progression of biliary fibrosis that is observed during chronic cholestatic liver diseases, such as primary sclerosing cholangitis. To date, there are no effective treatments for hepatic fibrosis. Several recent studies have demonstrated that the renin-angiotensin system (RAS) plays a key role in hepatic fibrosis. Therapies targeting the RAS may represent a promising paradigm for the prevention and treatment of hepatic fibrosis in the setting of chronic liver disease. In this review, we provide a comprehensive update on the role of RAS in the pathogenesis of hepatic fibrosis in both animal models and human studies. We will discuss the profibrotic mechanisms activated by the RAS and the cell types involved. Studies that have utilized angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors to modulate the RAS in order to ameliorate hepatic fibrosis will also be discussed. Although the cumulative evidence supports the potential for the use of ARBs and ACE inhibitors as treatment for hepatic fibrosis, extensive studies of the effectiveness of RAS therapeutics are necessary in patients with chronic liver disease.

An unexpectedly high prevalence of colonization with the intestinal spirochaete Brachyspira aalborgi amongst residents of the Indonesian island of Bali.

PCR assays designed to amplify DNA from the anaerobic intestinal spirochaete Brachyspira aalborgi were conducted on DNA extracted from 938 faecal samples from 469 residents on the Indonesian island of Bali. The individuals tested were sampled twice in one year and were from four rural villages, one peri-urban centre and the capital city, Denpasar. Overall, an unexpectedly high prevalence of colonization (24.7%) was found, with prevalence rates at different locations varying from a low of 15.6% at one village to 41.5% in the peri-urban centre. Comparison of prevalence rates at the two sampling times suggested that, in many individuals, colonization was likely to be prolonged (>3 months) and/or that reinfection was occurring frequently in these people. Analysis of a questionnaire administered to the individuals who were sampled identified specific risk factors for colonization as location, co-colonization with the related intestinal spirochaete Brachyspira pilosicoli and use of drinking water obtained from wells rather than from taps. No specific associations with clinical symptoms were identified.

Chlororespiratory reduction 6 is a novel factor required for accumulation of the chloroplast NAD(P)H dehydrogenase complex in Arabidopsis.

The chloroplast NAD(P)H dehydrogenase (NDH) complex is involved in photosystem I cyclic electron transport and chlororespiration in higher plants. An Arabidopsis (Arabidopsis thaliana) chlororespiratory reduction 6 (crr6) mutant lacking NDH activity was identified by means of chlorophyll fluorescence imaging. Accumulation of the NDH complex was impaired in crr6. Physiological characterization of photosynthetic electron transport indicated the specific defect of the NDH complex in crr6. In contrast to the CRR7 protein that was recently identified as a potential novel subunit of the NDH complex by means of the same screening, the CRR6 protein was stable under the crr2 mutant background in which the NDH complex does not accumulate. The CRR6 gene (At2g47910) encodes a novel protein without any known motif. Although CRR6 does not have any transmembrane domains, it is localized in the thylakoid membrane fraction of the chloroplast. CRR6 is conserved in phototrophs, including cyanobacteria, from which the chloroplast NDH complex has evolutionally originated, but not in Chlamydomonas reinhardtii, in which the NDH complex is absent. We believe that CRR6 is a novel specific factor for the assembly or stabilization of the NDH complex.

Identification of a novel protein, CRR7, required for the stabilization of the chloroplast NAD(P)H dehydrogenase complex in Arabidopsis.

An Arabidopsis thaliana mutant, crr7 (chlororespiratory reduction), was isolated using chlorophyll fluorescence imaging to detect reduced activity in NAD(P)H dehydrogenase (NDH). The chloroplast NDH complex is considered to have originated from cyanobacteria in which the NDH complex is involved in respiration, photosystem I (PSI) cyclic electron transport and CO2 uptake. In higher plants the NDH complex functions in PSI cyclic electron transport within the chloroplast. Despite exhaustive biochemical approaches, the entire subunit composition of the NDH complex is unclear in both cyanobacteria and chloroplasts. In crr7 accumulation of the NDH complex was specifically impaired. In vivo analysis of electron transport supported the specific loss of the NDH complex in crr7. CRR7 (At5g39210) encodes a protein of 156 amino acids, including a putative plastid target signal, and does not contain any known motifs. In contrast to CRR2 and CRR4, involved in the expression of chloroplast ndh genes, CRR7 is conserved in cyanobacterial genomes. Although CRR7 did not contain any transmembrane domains, it localized to the membrane fraction of the chloroplast. CRR7 was unstable in the crr2-2 mutant background, in which the expression of ndhB was impaired. These results strongly suggest that CRR7 is a novel subunit of the chloroplast NDH complex.