with at least some of the bidding systems that do not use the size of a cash bonus as the bidding variable.
1. California has standing to challenge the Secretary's choice of bidding systems. Because the 1978 Amendments require the Federal Government to turn over a fair share of the revenues of an OCS lease to the neighboring coastal State whenever the Federal Government and the State own adjoining portions of an OCS oil and gas pool, California has a direct financial stake in federal OCS leasing off the California coast. In alleging that the bidding systems currently used by the Secretary are incapable of producing a fair market return, California asserts the kind of "distinct and palpable injury" that is required for standing. And California also satisfies the requirement that there be a "fairly traceable" causal connection between the injury it claims and the conduct it challenges, so that, if the relief sought is granted, the injury will be redressed. Pp. 454 U. S. 160-162.
2. The Court of Appeals erred in compelling the Secretary to experiment with non-cash-bonus bidding systems. Pp. 454 U. S. 162-169.
(a) Nothing in the 1978 Amendments suggests that Congress, in committing the Government to the goal of obtaining fair market value for OCS oil and gas resources, intended to channel the Secretary's discretion in choosing among the alternative bidding systems, and nothing in the statute singles out the non-cash-bonus systems for special consideration. The language of the 1978 Amendments requires experimentation with at least some of the new bidding systems, but leaves the details to the Secretary's discretion. Pp. 454 U. S. 162-165.
(b) Nor does the legislative history of the 1978 Amendments compel the conclusion that the Congress as a whole intended to limit the Secretary's discretion to choose among the various experimental bidding systems. When viewed in context, unfavorable references to "cash bonus" bidding show congressional dissatisfaction with large front-end payments associated with the traditional cash bonus bid, fixed royalty system then in effect, not with all forms of cash bonus bidding. Pp. 454 U. S. 165-168.
210 U.S.App.D.C. 20, 654 F.2d 73, reversed.
We are asked to review a decision of the United States Court of Appeals for the District of Columbia Circuit compelling the Secretary of the Interior to experiment with the use of certain statutorily defined bidding systems in awarding leases for oil and gas exploration and development on the Outer Continental Shelf. Because the decision below incorrectly construes the Outer Continental Shelf Lands Act Amendments of 1978, 92 Stat. 629, 43 U.S.C. § 1331 et seq. (1976 ed. and Supp. III), we reverse.
fixing the amount of the cash bonus, and requiring bids on the royalty rate. 43 U.S.C. § 1337(a) . The OCS Lands Act vested complete discretion in the Secretary to choose between these two bidding systems. In practice, prior to 1978, virtually all tracts were leased on the basis of a fixed royalty of 16 2/3% of the gross value of production, with bidding on the amount of the cash bonus. See H.R.Rep. No. 9590, p. 138 (1977); S.Rep. No. 9284, p. 72 (1977).
During the mid-1970's, the Nation's increasing dependence on imported oil focused public attention on the OCS as a potential source of domestic petroleum and natural gas. See H.R.Rep. No. 95-590, supra, at 554. At the same time, the traditional OCS bidding procedures came under close scrutiny because dramatic increases in petroleum prices made existing cash bonuses seem miserly relative to the revenues generated from wells on OCS leaseholds. Members of Congress began to express reservations about the ability of the traditional cash bonus, fixed royalty system to assure a fair return to the Government, principally because it appeared that only the major oil companies could risk paying a large cash bonus to lease a tract of unknown value. Because the number of bidders was often limited to a handful of giant concerns, competition for the leases seemed tepid, and there was no assurance that the ultimate return to the Government was adequate. See, e.g., id. at 47, 54.
under [the 1978 Amendments], and why such system or systems should or should not be utilized."
This litigation grows out of the Secretary of the Interior's continued reliance on cash bonus bidding systems. The respondents here, nine consumer groups, two state governmental entities, and three private citizens, brought suit against the United States, the Secretary of the Interior and the Secretary of Energy, alleging that the Secretaries had abused their discretion by failing to experiment with bidding systems that do not use the size of a cash bonus as the bidding variable. In essence, they complained that bonus bidding cannot generate adequate competition to yield a fair market return for OCS oil and gas as required by the 1978 Amendments. They sought declaratory and injunctive relief prohibiting further lease sales until the Secretary of Energy promulgated regulations for each of the alternative bidding systems, and prohibiting the further use of the cash bonus, low royalty bidding systems.
Three days after they filed suit and four days before a planned lease sale, the respondents filed a motion for a preliminary injunction barring all further lease sales until regulations had been promulgated for each of the bidding options contained in the 1978 Amendments. The District Court denied the motion because the respondents had not shown a likelihood of prevailing on the merits, and because the pace at which the Secretary of Energy was issuing regulations was not unlawfully slow in light of the complexity involved in preparing such regulations. [Footnote 10] The Court of Appeals affirmed the District Court's ruling and remanded the case for further proceedings. Energy Action Educational Foundation v. Andrus, 203 U.S.App.D.C. 169, 631 F.2d 751 (1979).
On remand, both parties moved for summary judgment, and the respondents renewed their motion for a preliminary injunction barring future lease sales until additional bidding system regulations had been issued. The District Court denied all motions for summary judgment, as well as the respondents' motion for a preliminary injunction, 516 F.Supp. 90 (DC 1980), and the respondents once more appealed.
Educational Foundation v. Andrus, 210 U.S.App.D.C. 20, 654 F.2d 735 (1980).
We granted the Government's petition for certiorari to review this construction of the 1978 Amendments. 450 U.S. 1040.
There are three groups of plaintiffs in this litigation: (1) the State of California, which claims standing as an involuntary "partner" with the Federal Government in the leasing of OCS tracts in which the underlying pool of gas and oil lies under both the OCS and the 3-mile coastal belt controlled by California; (2) California and the city of Long Beach, which compete with the Federal Government in the leasing of off-shore oil and gas properties; and (3) consumers of oil and gas and of oil- and gas-derived products. [Footnote 12] Because we find California has standing, we do not consider the standing of the other plaintiffs. See Arlington Heights v. Metropolitan Housing Development Corp., 429 U. S. 252, 429 U. S. 264, and n. 9 (1977); Buckley v. Valeo, 424 U. S. 1, 424 U. S. 12 (1976) (per curiam).
pool. See 43 U.S.C. § 1337(g)(4) (1976 ed., Supp. III). California thus has a direct financial stake in federal OCS leasing off the California coast. In alleging that the bidding systems currently used by the Secretary of the Interior are incapable of producing a fair market return, California clearly asserts the kind of "distinct and palpable injury," Warth v. Seldin, 422 U. S. 490, 422 U. S. 501 (1975), that is required for standing.
To demonstrate that it has standing, however, California must also show that there is a "fairly traceable" causal connection between the injury it claims and the conduct it challenges, Arlington Heights v. Metropolitan Housing Development Corp., supra, at 429 U. S. 261, so that, if the relief sought is granted, the injury will be redressed, Simon v. Eastern Ky. Welfare Rights Org., 426 U. S. 26, 426 U. S. 41-46 (1976). The petitioners argue that the relief California seeks experimental use on some OCS lease tracts of non-cash-bonus bidding systems will not ensure that the Secretary will try these systems on parcels leased off the California coast. According to the petitioners, even if California were to win its suit, cash bonus systems might nevertheless still be used to lease tracts overlying California's pools. The petitioners assert that California therefore lacks standing because it has failed to show that the relief requested would cause the Secretary of the Interior to use non-cash-bonus bidding systems on California's parcels.
system proved by experiment to be superior to the cash bonus alternatives.
In passing the 1978 Amendments, Congress committed the Government to the goal of obtaining fair market value for OCS oil and gas resources. The 1978 Amendments themselves proclaim this intention, [Footnote 13] and the legislative history is replete with references to this purpose. [Footnote 14] The respondents urge that non-cash-bonus bidding systems are more likely to achieve the statutory objectives than the cash bonus systems used to date, so that the Secretary of the Interior's continued reliance on cash bonus bidding violates the statutory scheme.
of the 1978 Amendments, Congress not only failed to repudiate the traditional cash bonus, fixed royalty system specified in § 1337(a)(1)(A), but affirmatively directed that the Secretary of the Interior use that system in the bidding for tracts covering at least 40% of the total area leased in each year of the 5-year plan. § 1337(a)(5)(B). The only express limitation Congress put on the use of the traditional system was that it not be used on more than 80% of the total area offered each year. Ibid. In short, Congress can hardly be said to have rejected even the traditional cash bonus system. Moreover, among the experimental bidding alternatives listed in the 1978 Amendments, Congress expressly specified cash bonus as the bid variable in three systems. [Footnote 15] Most significantly, Congress left to "the discretion of the Secretary," § 1337(a)(1), the choice among the various nontraditional alternatives, evidently leaving,to his expert administrative determination the complex, technical problem of deciding which alternative bidding systems are more likely to further the statute's objectives. In addition, Congress granted the Secretary further discretion to abandon the statutory requirements for the percentage use of the nontraditional alternatives, should he determine that those requirements are inconsistent with the statutory purposes and policies. § 1337(a)(5)(B).
"[l]easing activities shall be conducted to assure receipt of fair market value for the lands leased and the rights conveyed by the Federal Government."
because cash bonus bidding allegedly does not assure that fair market value is received for the Government's resources.
much as 80%, and on no less than 40%, of the acreage leased. § 1337(a)(5)(B). So Congress cannot have considered the traditional cash bonus system incapable of providing a fair market return, for that is the one system Congress required the Secretary to use. We therefore conclude that § 1344(a)(4) cannot fairly be read to constrain indirectly the Secretary's discretion in choosing to use the alternative cash bonus bidding systems.
The only express statutory check on the Secretary of the Interior's discretion is the requirement that he periodically report to the Congress his reasons for failing to use any of the alternative bidding systems. [Footnote 17] The statute thus recognizes that, in appropriate circumstances, some of the alternative bidding systems may not be used. Plainly, Congress considered close congressional scrutiny to be sufficient restraint on the Secretary's discretion to choose among the statutory options.
the statute. In particular, the respondents cite the repeated, unfavorable references to "cash bonus" bidding found throughout the legislative history to support their contention that Congress intended to direct the Secretary of the Interior to experiment with bidding systems in which the bidding variable is not the size of a cash bonus.
Such a reduction of the front-end payments can be achieved, however, with any bidding system that increases the amount of the payments made throughout the life of a lease, since a bidder will be willing to pay less "up front" if he expects to pay more "downstream." This inverse relationship between the size of up-front and downstream payments holds true, of course, regardless of which factor is used as a bidding variable. Congress plainly understood this relationship, because it expressly included three new cash bonus bid systems among the experimental alternatives intended to reduce large front-end payments.
Secretary of the Interior is well advised to forgo experimentation with the non-cash-bonus alternatives. That question is for Congress alone to answer in the exercise of its oversight powers.
"all submerged lands lying seaward and outside of the area of lands beneath navigable waters . . . and of which the subsoil and seabed appertain to the United States and are subject to its jurisdiction and control."
43 U.S.C. § 1331(a). The term "lands beneath navigable waters" is itself given an extensive definition in 43 U.S.C. 1301, but generally means the undersea lands within three miles of the coastline.
The "basic purpose" of the 1978 Amendments was to "promote the swift, orderly and efficient exploitation of our almost untapped domestic oil and gas resources in the Outer Continental Shelf," H.R.Rep. No. 95-590, p. 53 (1977), and the Amendments were broadly designed to achieve that aim. We are concerned here, however, only with those provisions of the 1978 Amendments having to do with bidding systems for OCS leases.
Title 43 U.S.C. § 1337(a)(1) (1976 ed., Supp. III) authorizes: (1) a "cash bonus bid with a royalty at not less than 12 1/2 per centum fixed by the Secretary in amount or value of the production saved, removed, or sold," § 1337(a)(1)(A); (2) a "cash bonus bid . . . and a diminishing or sliding royalty based on such formulae as the Secretary shall determine as equitable to encourage continued production from the lease area as resources diminish, but not less than 121/2 per centum at the beginning of the lease period in amount or value of the production saved, removed, or sold," § 1337(a)(1)(C); (3) a "cash bonus bid with a fixed share of the net profits of no less than 30 per centum to be derived from the production of oil and gas from the lease area," § 1337(a)(1)(D); and (4) a "cash bonus bid with a royalty at no less than 12 1/2 per centum fixed by the Secretary in amount or value of the production saved, removed, or sold and a fixed per centum share of net profits of no less than 30 per centum to be derived from the production of oil and gas from the lease area," § 1337(a)(1)(F).
"variable royalty bid based on a per centum in amount or value of the production saved, removed, or sold, with either  a fixed work commitment based on dollar amount for exploration or  a fixed cash bonus as determined by the Secretary, or  both."
Section 1337(a)(1)(E) authorizes a "fixed cash bonus with the net profit share reserved as the bid variable."
Section 1337(a)(1) authorizes: (1) a "work commitment bid based on a dollar amount for exploration with a fixed cash bonus, and a diminishing or sliding scale royalty based on such formulae as the Secretary shall determine as equitable to encourage continued production from the lease area as resources diminish, but not less than 12 1/2 per centum at the beginning of the lease period in amount or value of the production saved, removed, or sold," § 1337(a)(1)(C); and (2) a "work commitment bid based on a dollar amount for exploration with a fixed cash bonus and a fixed royalty in amount or value of the production saved, removed, or sold," § 1337(a)(1)(G).
Section 1337(a)(9)(E) requires that his determination be explained to Congress.
Under the 1978 Amendments, the Secretaries of the Interior and of Energy work together on the OCS leasing program. Competitive bidding for OCS leases is to be carried out pursuant to "regulations promulgated in advance," § 1337(a)(1), and the Department of Energy Organization Act, 42 U.S.C. §§ 7152(b), 7153 (1976 ed., Supp. III), gives the Secretary of Energy the responsibility for issuing such regulations in consultation with the Secretary of the Interior. The Secretary of Energy also has authority to develop bidding systems other than the 10 specifically enumerated in § 1337(a)(1), provided any new system has no more than one bidding variable and is not disapproved by Congress. §§ 1337(a)(1)(H), (a)(4)(A).
During the course of the present litigation, the Secretary of the Interior filed an affidavit with the District Court stating that he does not intend to use either profit-share or work-commitment bidding because he does "not believe the purposes of the OCS Lands Act or the best interests of the nation would be served by the use" of either system. Affidavit of James G. Watt, Secretary of the Interior, Energy Action Educational Foundation v. Watt, No. 79-1633 (DC) (sworn May 8, 1981), reprinted in App. to Brief for Respondents 2a-3a. The Department of the Interior is on record as disfavoring royalty-share bidding as well. See Energy Action Educational Foundation v. Andrus, 210 U.S.App.D.C. 20, 28, and n. 44, 654 F.2d 735, 743, and n. 44 (1980).
479 F.Supp. 62 (DC 1979).
On remand to the District Court, the parties stipulated to the entry of an order requiring the Department of Energy to issue final regulations for the net profit-share bid, fixed cash bonus system and the work-commitment bid, fixed cash bonus and fixed royalty system. Brief for Petitioners 9; Brief for Respondents 5, n. 1; see also 46 Fed.Reg. 35614, 35615 (1981) (to be codified in 10 CFR §§ 376, 390). Thus, no question is now presented concerning the Secretary of Energy's duty to issue these regulations. The Court of Appeals and the respondents based their conclusion that the Secretary of Energy must issue regulations for the alternative systems on the theory that the Secretary of the Interior must use them, the issue under consideration here.
In their initial complaint, the individual respondents also claimed standing as taxpayers, but have not pressed that claim here. The 1978 Amendments contain a provision which permits suit by those having "a valid legal interest." § 1349(a)(1).
Section 1344(a)(4) states that "[l]easing activities shall be conducted to assure receipt of fair market value for the lands leased and the rights conveyed by the Federal Government."
See, e.g., H.R.Rep. No. 95-590, pp. 47, 54 (1977); S.Rep. No. 9284, pp. 46, 73 (1977).
Those three are the cash bonus bid, diminishing or sliding-scale royalty system, § 1337(a)(1)(C), the cash bonus bid, fixed net profit-share system, § 1337(a)(1)(D), and the cash bonus bid, fixed royalty and fixed net profitshare system, § 1337(a)(1)(F).
"The conferees intend that, in utilizing the new bidding alternatives, a variety of considerations should be taken into account, including but not limited to: (i) Providing a fair return to the Federal Government; (ii) increasing competition; (iii) assuring competent and safe operations; (iv) avoiding undue speculation; (v) avoiding unnecessary delays in exploration, development, and production; (vi) discovering and recovering oil and gas; (vii) developing new oil and gas resources in an efficient and timely manner; and (viii) limiting administrative burdens on government and industry."
H.R.Conf.Rep. No. 91474, p. 92 (1978).
"One purpose of [the 1978 Amendments] is to authorize alternative leasing arrangements and require experimentation with them. It will enable the Secretary of the Interior, who administers the federal leasing program, to strike a proper balance between securing a fair return to the Federal Government for the lease of its lands, increasing competition in exploitation of resources, and providing the incentive of a fair profit to the oil companies, which must risk their investment capital."
H.R.Rep. No. 95 590, p. 54 (1977).
Section 1337(a)(9)(D) requires the Secretary of Energy, in consultation with the Secretary of the Interior, to report to Congress "why a particular bidding system has not been or will not be utilized." Section 1343(2)(A) requires the Secretary of the Interior to report to Congress "the reasons why a particular bidding system has not been utilized."
"S. 9 authorizes a wide variety of new bidding systems. These are designed to reduce the front end cash bonus, increase the government's return on actual production of oil or gas, make it easier for smaller companies to enter the OCS development business, and increase the availability of funds for exploration."
"In order to assure that these alternatives will be used, the bill limits the Secretary's authority to use the cash bonus-fixed royalty system which has been the historical method of OCS bidding. . . . "
"At present, the cash bonus system is used almost exclusively. Under that system, in order to win a lease, a company must have vast amounts of capital, and the price to the company is set without full knowledge of the value of the oil and gas in the area. This may reduce competition for offshore leases to the major oil companies and reduce the public return for resources. To increase competition for off-shore lease and secure higher returns to the public Treasury, section 8 of the Outer Continental Shelf Lands Act has been amended to allow the Secretary to use other bidding methods based on net profits; royalty; or work commitments stated in dollar amounts."
"Witnesses before the committee indicated that the high front-end bonus bids may have created a barrier to the entry of small and medium-sized oil firms as well as other potential exploiters, to the OCS activity, and that these types of bids do not, after the completion of exploitation of a lease area, provide a fair return to the Government."
"[T]he 1977 amendments authorizes [sic] new bidding options. The basic thrust of all these new options is to reduce the reliance on large front-end cash bonuses as the means of obtaining a fair price for the public's property. . . ."
"In order to assure that these new bidding alternatives are used, the 1977 amendment limit the Secretary's authority to use the cash bonus -- fixed royalty system, which has been the historical method of OCS bidding."
"Bidding systems other than bonus bidding, including royalty, net profit, work commitment, and nonenumerated systems, are to be utilized in at least 20 percent and not more than 60 percent of the tracts offered for leasing in all OCS areas during each of the next 6 years."
(Emphasis in original.) Plainly, the reference to "bonus bidding" is to the traditional system specified in § 1337(a)(1)(A). Otherwise, the summary is simply wrong, because three of the enumerated alternatives retain the size of a cash bonus as the bidding variable. Similar examples are found throughout the legislative history. See H.R.Rep. No. 96-690, pp. 47, 138-139, 141 (1977); S.Rep. No. 96-284, pp. 447 (1977); H.R.Conf.Rep. No. 96-1474, supra, at 93.


Appeal of S.C., on behalf of her children A.C. and A.C., from action of the Board of Education of the Elmont Union Free School District regarding immunization.
ELIA., Commissioner.--Petitioner appeals the determination of the Board of Education of the Elmont Union Free School District (“respondent”) that her children, A.C. and A.C. (“the students”), are not entitled to religious exemptions from the immunization requirements of Public Health Law (“PHL”) §2164. The appeal must be sustained in part and remanded.
In a letter dated November 8, 2017, respondent denied the requests, without stating a reason for the denial. This appeal ensued.
Petitioner argues that the denial of her requests was arbitrary and capricious because respondent did not adequately consider her requests and failed to articulate its reasoning for the denial.
Respondent counters that it properly denied petitioner’s requests after careful consideration.
Proof of immunization against certain diseases is generally required for a child to be admitted to school (PHL §2164). However, evidence of immunization is not required if a child’s parent or guardian holds genuine and sincere religious beliefs contrary to the mandated immunizations (PHL §2164).
The determination of whether a petitioner qualifies for a religious exemption requires careful consideration of two factors: whether his or her purported beliefs are religious and, if so, whether such religious beliefs are genuinely and sincerely held (Farina v. Bd. of Educ. of the City of New York, et al., 116 F.Supp 2d 503). It is not necessary for persons to be members of a recognized religious organization whose teachings oppose inoculation to claim the statutory exemption (Sherr, et al. v. Northport-East Northport Union Free School District, et al., 672 F.Supp 81). However, the exemption does not extend to persons whose views are founded upon medical or purely moral considerations, scientific or secular theories, or philosophical and personal beliefs (Farina v. Bd. of Educ. of the City of New York, et al., 116 F.Supp 2d 503).
Whether a religious belief is sincerely held can be a difficult factual determination that must be made, in the first instance, by school district officials (Appeal of S.F. and E.R., 58 Ed Dept Rep, Decision No. 17,439; Appeal of T.R., 57 id., Decision No. 17,329; Appeal of H.A., 57 id., Decision No. 17,215). A parent or guardian who seeks a religious exemption must submit a written and signed statement to the school district stating that the parent or guardian objects to the child’s immunization due to sincere and genuine religious beliefs which prohibit the immunization of the child (10 NYCRR §66-1.3[d]). If, after reviewing the parental statement, questions remain about the existence of a sincerely held religious belief, the principal or person in charge of a school may request supporting documents (10 NYCRR §66-1.3[d]).
In determining whether beliefs are religious in nature and sincerely held, school officials must make a good faith effort to assess the credibility and sincerity of the parent or guardian’s statements and may consider the parent or guardian’s demeanor and forthrightness. While school officials are not required to simply accept a statement of religious belief without some explanation, they similarly should not simply reject a statement without further examination (Appeal of S.F. and E.R., 58 Ed Dept Rep, Decision No. 17,439; Appeal of D.G. and B.L., 57 id., Decision No. 17,345; Appeal of T.R., 57 id., Decision No. 17,329).
Initially, petitioner asserts that respondent failed to provide a sufficient explanation of the reasons for denying her requests for religious exemptions. In support of her claim, petitioner relies on guidance from the New York State Education Department (“Department”), which states that a decision to deny a request for a religious exemption must be in writing and “the written communication must address the specific reasons for the denial; merely stating that the request does not demonstrate a sincerely-held religious belief is not sufficient articulation.” In this case, despite respondent’s protestations to the contrary, the record reflects that respondent did not fully consider petitioner’s requests. In her letters requesting the religious exemptions, petitioner made only very general allegations that her religious beliefs prohibit the injection of foreign particles into the body and immunizations “are a lack of faith in God” and God’s perfect immune system. Respondent’s September 1, 2017 letter stated that petitioner’s religious beliefs did not require an exemption from immunization and explained that, in respondent’s judgment, petitioner’s statement was “formed” in terms of religious belief to gain an exemption. While ambiguous, the September 1, 2017 letter appears to reflect respondent’s contention that petitioner’s objections to immunizations are not religious in nature, but rather are grounded in her concerns about the harmful effects of immunization. Such contention is clearly set forth in the answer in this appeal. However, respondent’s December 4, 2017 letter, which again denied petitioner’s requests, does not address petitioner’s allegations in her October 31, 2017 email concerning her religious objections over the use of cells from aborted fetal tissue and other contaminants in immunizations. Respondent’s answer is completely silent on this issue. Thus, respondent did not fully address petitioner’s contentions and a remand is appropriate (see Appeal of M.S., 58 Ed Dept Rep, Decision No. 17,572; Appeal of L.B., 58 id., Decision No. 17,552).
I, therefore, remand this case to respondent to fully comply with the procedural requirements of PHL §2146 and determine, based upon an examination of petitioner’s beliefs, whether or not A.C. and A.C. are entitled to an exemption from the immunization requirements of PHL §2164 in conformity with all applicable law and regulations and consistent and in accordance with this decision and order and, in making such determination, respondent shall consider all relevant information submitted by petitioner.
In light of this disposition, I need not consider the parties’ remaining contentions.
THE APPEAL IS SUSTAINED TO THE EXTENT INDICATED AND REMANDED.
IT IS ORDERED that, within 30 days of this decision and order, respondent determine whether the students are entitled to an exemption from the immunization requirements of PHL §2164 in conformity with all applicable laws and regulations and consistent with this decision, and that, in making such determination, respondent shall consider all relevant information submitted by petitioner.


text:
Cysteine proteinases of microorganisms and viruses by G. N. Rudenskaya; D. V. Pupov (1-13).
This review considers properties of secreted cysteine proteinases of protozoa, bacteria, and viruses and presents information on the contemporary taxonomy of cysteine proteinases. Literature data on the structure and physicochemical and enzymatic properties of these enzymes are reviewed. High interest in cysteine proteinases is explained by the discovery of these enzymes mostly in pathogenic organisms. The role of the proteinases in pathogenesis of several severe diseases of human and animals is discussed.
Interaction of bd-type quinol oxidase from Escherichia coli and carbon monoxide: Heme d binds CO with high affinity by V. B. Borisov (14-22).
Comparative studies on the interaction of the membrane-bound and detergent-solubilized forms of the enzyme in the fully reduced state with carbon monoxide at room temperature have been carried out. CO brings about a bathochromic shift of the heme d band with a maximum at 644 nm and a minimum at 624 nm, and a peak at 540 nm. In the Soret band, CO binding to cytochrome bd results in absorption decrease and minima at 430 and 445 nm. Absorption perturbations in the Soret band and at 540 nm occur in parallel with the changes at 630 nm and reach saturation at 3–5 μM CO. The peak at 540 nm is probably either β-band of the heme d-CO complex or part of its split α-band. In both forms of cytochrome bd, CO reacts predominantly with heme d. Addition of high CO concentrations to the solubilized cytochrome bd results in additional spectral changes in the γ-band attributable to the reaction of the ligand with 10–15% of low-spin heme b 558. High-spin heme b 595 does not bind CO even at high concentrations of the ligand. The apparent dissociation constant values for the heme d-CO complex of the membrane-bound and detergent-solubilized forms of the fully reduced enzyme are about 70 and 80 nM, respectively.
Structural trees for proteins containing φ-motifs by A. V. Efimov (23-28).
In the present study, a novel structural motif of proteins referred to as the φ-motif is considered, and two novel structural trees in which the φ-motif is taken as the root structure have been constructed. The simplest φ-motif is formed by three adjacent β-strands connected by loops and packed in one β-sheet so that its overall fold resembles the Greek letter φ. Construction of the structural trees and modeling of folding pathways have shown that all structures of the protein superfamilies can be obtained by stepwise addition of α-helices and/or β-strands to the root φ-motif taking into account a restricted set of rules inferred from known principles of protein structure. The structural trees are a good tool for structure comparison, structural classification of proteins, as well as for searching for all possible protein folds and folding pathways.
Role of P-glycoprotein in evolution of populations of chronic myeloid leukemia cells treated with imatinib by T. P. Stromskaya; E. Yu. Rybalkina; S. S. Kruglov; T. N. Zabotina; E. B. Mechetner; A. G. Turkina; A. A. Stavrovskaya (29-37).
Imatinib mesylate (imatinib) is a new generation preparation that is now successfully used for treatment of cancer, particularly for chemotherapy of chronic myeloid leukemia (CML). Imatinib inhibits the activity of chimeric kinase BCR-ABL, which is responsible for the development of CML. The goal of this study was to investigate the role of a multidrug resistance protein, P-glycoprotein (Pgp), in the evolution of CML treated with imatinib. We demonstrate here that although imatinib is a substrate for Pgp, cultured CML cells (strain K562/i-S9), overexpressing active Pgp, do not exhibit imatinib resistance. Studies of CML patients in the accelerated phase have shown variations in the number of Pgp-positive cells (Pgp+) among individual patients treated with imatinib. During treatment of patients with imatinib for 6–12 months, the number of Pgp-positive cells significantly increased in most patients. The high number of Pgp+ cells remained in patients at least for 4.5 years and correlated with active Rhodamine 123 (Rh123) efflux. Such correlation was not found in the group of imatinib-resistant patients examined 35–60 months after onset of imatinib therapy: cells from the imatinibresistant patients exhibited efficient Rh123 efflux irrespectively of Pgp expression. We also compared the mode of Rh123 efflux by cells from CML patients who underwent imatinib treatment for 6–24 months and the responsiveness of patients to this therapy. There were significant differences in survival of patients depending on the absence or the presence of Rh123 efflux. In addition to Pgp, patients’ cells expressed other transport proteins of the ABC family. Our data suggest that treatment with imatinib causes selection of leukemic stem cells characterized by expression of Pgp and other ABC transporters.
Identification of a novel nuclear-localized adenylate kinase from Drosophila melanogaster by Geng Meng; Ruitong Zhai; Bin Liu; Xiaofeng Zheng (38-43).
As a step to further understand the role of adenylate kinase (AK) in the energy metabolism network, we identified, purified, and characterized a previously underscribed adenylate kinase in Drosophila melanogaster. The cDNA encodes a 175-amino acid protein, which shows 47.85% identity in 163 amino acids to human AK6. The recombinant protein was successfully expressed in Escherichia coli BL21 (DE3) strain. Characterization of this protein by enzyme activity assay showed adenylate kinase activity. AMP and CMP were the preferred substrates, and UMP can also be phosphorylated to some extent, with ATP as the best phosphate donor. Subcellular localization study showed a predominantly nuclear localization. Therefore, based on the substrate specificity, the specific nuclear localization in the cell, and the sequence similarity with human AK6, we named this novel adenylate kinase identified from the fly DAK6.
Complete sequencing of potato virus X new strain genome and construction of viral vector for production of target proteins in plants by N. V. Ravin; E. S. Mardanova; R. Yu. Kotlyarov; V. K. Novikov; J. G. Atabekov; K. G. Skryabin (44-49).
The complete nucleotide sequence of the genome of a new potato virus X (PVX) strain Tula isolated by us has been determined. Based on comparison of the PVX Tula nucleotide sequence with the sequences of 12 other PVX strains, this strain was assigned to the European cluster of PVX strains. Phylogenetic analysis revealed the same phylogeny for both full genome sequences and nucleotide sequences of polymerase and coat protein genes, suggesting that the PVX evolution did not involve recombination between different strains. The full-size cDNA copy of the PVX Tula genome was cloned and the accumulation of the viral coat protein in infected Nicotiana benthamiana was shown to be about twofold higher than for the PVX strain UK3. Based on the PVX Tula genome, a new vector which contained the target gene instead of the removed triple transport gene block and the coat protein gene has been constructed for expression of target proteins in plants. The productivity of the new vector was about 1.5–2-fold higher than the productivity of the vector of the same structure based on the standard PVX strain genome. The new viral vector can be used for superproduction of recombinant proteins in plants.
Oligomerization of the potato virus X 25-kD movement protein by A. D. Leshchiner; E. A. Minina; D. V. Rakitina; V. K. Vishnichenko; A. G. Solovyev; S. Yu. Morozov; N. O. Kalinina (50-55).
A 25-kD movement protein (25K protein) encoded by the first gene of the potexvirus Potato virus X triple gene block of transport genes is essential for the viral movement in infected plants. The 25K protein belongs to superfamily 1 of NTPase/helicases and exhibits in vitro RNA helicase, Mg2+-dependent NTPase, and RNA-binding activities. In the present work, the ability of 25K protein for homologous interactions was studied using the yeast two-hybrid system, protein chemical cross-linking in the presence of glutaraldehyde, far-Western blotting, and ultracentrifugation in sucrose density gradients. The 25K protein was shown to form homodimers and homooligomers. Sites of homologous protein-protein interactions were found in both the N- and C-terminal portions of the protein.
Molecular modeling studies of substrate binding by penicillin acylase by G. G. Chilov; O. V. Stroganov; V. K. Švedas (56-64).
Molecular modeling has revealed intimate details of the mechanism of binding of natural substrate, penicillin G (PG), in the penicillin acylase active center and solved questions raised by analysis of available X-ray structures, mimicking Michaelis complex, which substantially differ in the binding pattern of the PG leaving group. Three MD trajectories were launched, starting from PDB complexes of the inactive mutant enzyme with PG (1FXV) and native penicillin acylase with sluggishly hydrolyzed substrate analog penicillin G sulfoxide (1GM9), or from the complex obtained by PG docking. All trajectories converged to a similar PG binding mode, which represented the near-to-attack conformation, consistent with chemical criteria of how reactive Michaelis complex should look. Simulated dynamic structure of the enzyme-substrate complex differed significantly from 1FXV, resembling rather 1GM9; however, additional contacts with residues bG385, bS386, and bN388 have been found, which were missing in X-ray structures. Combination of molecular docking and molecular dynamics also clarified the nature of extremely effective phenol binding in the hydrophobic pocket of penicillin acylase, which lacked proper explanation from crystallographic experiments. Alternative binding modes of phenol were probed, and corresponding trajectories converged to a single binding pattern characterized by a hydrogen bond between the phenol hydroxyl and the main chain oxygen of bS67, which was not evident from the crystal structure. Observation of the trajectory, in which phenol moved from its steady bound to pre-dissociation state, mapped the consequence of molecular events governing the conformational transitions in a coil region a143-a146 coupled to substrate binding and release of the reaction products. The current investigation provided information on dynamics of the conformational transitions accompanying substrate binding and significance of poorly structured and flexible regions in maintaining catalytic framework.
Polyphosphates and exopolyphosphatases in cytosol and mitochondria of Saccharomyces cerevisiae during growth on glucose or ethanol under phosphate surplus by N. A. Andreeva; T. V. Kulakovskaya; E. V. Kulakovskaya; I. S. Kulaev (65-69).
Content and chain lengths of inorganic polyphosphates (polyP) as well as exopolyphosphatase activities were compared in cytosol and mitochondria of the yeast Saccharomyces cerevisiae during growth on glucose or ethanol under phosphate surplus. PolyP metabolism in cytosol and mitochondria was substantially dependent upon the carbon source. Acid-soluble polyP accumulated mainly in cytosol using either glucose or ethanol. The level of the accumulation was lower during growth on ethanol compared to that on glucose. Increase in polyP content in mitochondria was observed during growth on glucose, but not on ethanol. In cytosol the activity of exopolyphosphatase PPN1 was increased and the activity of exopolyphosphatase PPX1 was decreased independently of the carbon source under phosphate surplus conditions. Growth on ethanol caused exopolyphosphatase PPN1 to appear in the soluble mitochondrial fraction, while during growth on glucose only exopolyphosphatase PPX1 was present in this fraction.
Detection of target genes of FOXA transcription factors involved in proliferation control by L. O. Bryzgalov; N. I. Ershov; D. Yu. Oshchepkov; V. I. Kaledin; T. I. Merkulova (70-75).
To reveal the mechanism of tumor-suppressing activity of FOXA proteins in liver, a search for potential target genes of these transcription factors involved in proliferation control was carried out. In the first step, we have used data from the literature concerning gene expression in mouse liver (high content of FOXA proteins) and kidney (FOXA expression is absent) obtained by hybridization on microchips. A search for FOXA binding sites in regulatory regions of forty differentially expressing genes involved in proliferation control was carried out using the computer method SITECON. Eleven genes containing clusters of potential FOXA sites incorporating 3–6-fold repeats of TTTG were revealed. The FOXA-specific interaction with such microsatellite sites was confirmed by gel-retardation technique using the GST-fused protein containing the DNA-binding domain of FOXA2. Six genes containing clusters of confirmed binding sites—Cul2, Cdc73, Ptk, Pdcd, Creb, and Ppp2r5d—were selected. The effect of hepatocarcinogen orthoaminoazotoluene (OAT), which lowers the FOXA activity, on expression of these genes was studied by the real-time PCR. OAT was shown to increase sharply the level of mRNA of the Cul2 and Cdc73 genes.
Effects of lipoic acid on citrate content, aconitate hydratase activity, and oxidative status during myocardial ischemia in rats by A. V. Makeeva; T. N. Popova; L. V. Matasova; I. N. Yama (76-79).
The effects of lipoic acid on intensity of free radical reactions, citrate content, and aconitate hydratase during myocardial ischemia have been investigated. Treatment with lipoic acid normalized biochemiluminescence parameters and citrate level, which were increased in the myocardial pathology. Treatment with lipoic acid also increased specific activity of aconitate hydratase, which was decreased in myocardium and blood of animals with myocardial ischemia. Administration of lipoic acid decreased DNA fragmentation observed during myocardial ischemia. The data suggest that lipoic acid can be effectively used as a cardioprotector preventing the development of free radical oxidation during myocardial ischemia.
Investigation of enzymatic degradation of pectin polysaccharides under limiting conditions by N. Yu. Selivanov; I. V. Sorokina; O. G. Selivanova; O. I. Sokolov; V. V. Ignatov (80-86).
The dynamics of changes in spectra of oligosaccharide fragments formed during enzymatic degradation of plant pectins at low enzyme/substrate ratio was studied. It is shown that degradation of deesterified pectin molecules is a discrete and determined process manifested in establishment of a stable polysaccharide spectrum. It is noted that introduction of chemical modifications into the polysaccharide substrate structure preserves the discreteness of the polymer molecule fragmentation but changes the spectrum of formed oligosaccharide fragments. It is supposed that degradation is defined by the spatial (three-dimensional) organization of the polysaccharide molecule.
An essential tryptophan residue in alkaline phosphatase from pearl oyster (Pinctada fucata) by Li-Ping Xie; Guang-Rui Xu; Wei-Zhong Cao; Jin Zhang; Rong-Qing Zhang (87-91).
Alkaline phosphatases are ubiquitous enzymes found in most species including the pearl oyster, Pinctada fucata, where it is presumably involved in nacreous biomineralization processes. In the present study, we have purified alkaline phosphatases from the pearl oyster and modified the tryptophan residues using N-bromosuccinimide (NBS). We show that the resulting inactivation of purified alkaline phosphatase by NBS is dependent on modification of only one of five tryptophan residues in the enzyme. Substrate protection experiments showed that the tryptophan residue was not located at the substrate-binding site but was involved in the catalytic activity.
Mechanism of inhibition of catalase by nitro and nitroso compounds by V. Yu. Titov; Yu. M. Petrenko; A. F. Vanin (92-96).
Dinitrosyl iron complexes (DNIC) with thiolate ligands and S-nitrosothiols, which are NO and NO+ donors, share the earlier demonstrated ability of nitrite for inhibition of catalase. The efficiency of inhibition sharply (by several orders in concentration of these agents) increases in the presence of chloride, bromide, and thiocyanate. The nitro compounds tested—nitroarginine, nitroglycerol, nitrophenol, and furazolidone—gained the same inhibition ability after incubation with ferrous ions and thiols. This is probably the result of their transformation into DNIC. None of these substances lost the inhibitory effect in the presence of the well known NO scavenger oxyhemoglobin. This fact suggests that NO+ ions rather than neutral NO molecules are responsible for the enzyme inactivation due to nitrosation of its structures. The enhancement of catalase inhibition in the presence of halide ions and thiocyanate might be caused by nitrosyl halide formation. The latter protected nitrosonium ions against hydrolysis, thereby ensuring their transfer to the targets in enzyme molecules. The addition of oxyhemoglobin plus iron chelator o-phenanthroline destroying DNIC sharply attenuated the inhibitory effect of DNIC on catalase. o-Phenanthroline added alone did not influence this effect. Oxyhemoglobin is suggested to scavenge nitrosonium ions released from decomposing DNIC, thereby preventing catalase nitrosation. The mixture of oxyhemoglobin and o-phenanthroline did not affect the inhibitory action of nitrite or S-nitrosothiols on catalase.
Isolation and characterization of extracellular α-galactosidases from Penicillium canescens by O. A. Sinitsyna; E. A. Fedorova; I. M. Vakar; E. G. Kondratieva; A. M. Rozhkova; L. M. Sokolova; T. M. Bubnova; O. N. Okunev; A. M. Chulkin; Y. P. Vinetsky; A. P. Sinitsyn (97-106).
Two α-galactosidases were purified to homogeneity from the enzymatic complex of the mycelial fungus Penicillium canescens using chromatography on different sorbents. Substrate specificity, pH-and temperature optima of activity, stability under different pH and temperature conditions, and the influence of effectors on the catalytic properties of both enzymes were investigated. Genes aglA and aglC encoding α-galactosidases from P. canescens were isolated, and amino acid sequences of the proteins were predicted. In vitro feed testing (with soybean meal and soybean byproducts enriched with galactooligosaccharides as substrates) demonstrated that both α-galactosidases from P. canescens could be successfully used as feed additives. α-Galactosidase A belonging to the 27th glycosyl hydrolase family hydrolyzed galactopolysaccharides (galactomannans) and α-galactosidase C belonging to the 36th glycosyl hydrolase family hydrolyzed galactooligosaccharides (stachyose, raffinose, etc.) of soybean with good efficiency, thus improving the digestibility of fodder.
Study of redox potential in cytochrome c covalently bound to terminal oxidase of alkaliphilic Bacillus pseudofirmus FTU by M. S. Muntyan; D. A. Bloch (107-111).
Spectroelectrochemistry was used to determine the midpoint redox potentials of heme cofactors of the caa 3-type cytochrome oxidase from the alkaliphilic bacterium Bacillus pseudofirmus FTU. The apparent midpoint potentials (E m app ) for the most prominent transitions of hemes a and a 3 (+193 and +334 mV, respectively) were found to be similar to the values reported for other enzymes with high homology to the caa 3-type oxidase. In contrast, the midpoint potential of the covalently bound cytochrome c (+89 mV) was 150–170 mV lower than in cytochromes c, either low molecular weight or covalently bound to the caa 3 complex in all known aerobic neutralophilic and thermo-neutralophilic bacteria. Such an unusually low redox potential of the covalently bound cytochrome c of the caa 3-type oxidase of alkaliphilic bacteria, together with high redox potentials of hemes a and a 3, ensures more than twice higher difference in redox potentials inside the respiratory complex compared to the homologous mitochondrial enzyme. The energy released during this redox transition might be stored in the transmembrane H+ gradient even under low Δp in the alkaline environment of the bacteria at the expense of a significant increase in ΔG of the coupled redox reaction.
Cooperation of photosystem I with the plastoquinone pool in oxygen reduction in higher plant chloroplasts by B. N. Ivanov (112-118).
The possible functions of a light-induced electron transfer to oxygen in the photosynthetic electron transport chain of higher plant chloroplasts are considered. The thermodynamic preconditions, as well as the experimental data about the participations of ferredoxin, the components of photosystems I and II, and plastoquinone in oxygen reduction are examined. It is concluded that, even in the presence of ferredoxin and ferredoxin + NADP+, oxygen reduction is carried out mainly by the membrane-bound carriers of the photosynthetic electron transport chain. The hypothesis is put forward that most superoxides, which are produced by reduction of O2 molecules by the intramembrane components of the acceptor side of photosystem I, are reduced within the membrane by the plastohydroquinone molecules to the hydrogen peroxide. It is assumed that the H2O2 molecules that originate as the result of this process serve for signaling about the redox state of the plastoquinone pool.

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We perform a numerical simulation study of hollow-core anti-resonant reflection optical waveguides (ARROWs) fabricated using lithography and material deposition in the context of their suitability as a platform for on-chip photonic quantum information processing. We explore the effects of the core size, the number of pairs of anti-resonant layers surrounding the hollow core, and the refractive index contrast between the anti-resonant layer materials on propagation losses in the waveguide. Additionally, we investigate the feasibility of integrating these waveguides with Bragg gratings and dielectric metasurfaces to form on-chip cavities that could act as nonlinear optical elements controllable with single photons when loaded with atomic ensembles.
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Fig. 1 Schematic drawing of the cross sections of an ARROW: (a) lengthwise; transverse cross section of (b) a conventional hollow-core self-aligned pedestal ARROW that has a high index layer beneath the core (n1 > n2) and (c) a hollow-core self-aligned pedestal ARROW that has a low index layer beneath the core; (d) conceptual vision of an integrated opto-electronic system combining an ARROW loaded with atomic or molecular vapor with a Bragg grating and micro-wires that could be used to, e.g., generate magnetic field.
Fig. 2 Numerical simulation (a) of the transverse profile of the fundamental waveguide mode and (b) of the propagation loss spectrum of a hollow-core ARROW with a 5.8µm × 12µm core surrounded by 3 pairs of Si3N4(1.74)/SiO2 cladding layers arranged as shown in Fig. 1(b), designed and optimized for a wavelength of 852 nm. (c) Numerical simulation of propagation losses in waveguides optimized for 852 nm light with assorted hollow core sizes and three pairs of of Si3N4(1.74)/SiO2 cladding layers as shown in Fig. 1(b). (d) Effects of the number of cladding layer pairs and of the refractive index contrast between the two materials forming each pair on the simulated propagation losses for waveguides with 5.8µm × 12µm hollow cores. The square data points correspond to the cladding layers arranged as shown in Fig. 1(b), while the triangular data points represent cladding layers arranged as shown in Fig. 1(c). The value in brackets denotes the refractive index of the cladding layer material.
Fig. 3 (a) Etched gratings in the various anti-resonant layers: first layer above the core (left), first layer beneath the core (middle), and the top layer (right). (b) Change in the effective index of propagation Δneff for a hollow-core ARROW with 5.8µm × 12µm core surrounded by three pairs of Si3N4(1.74)/SiO2 cladding layers. The x-axis refers to the etch depth δt relative to the original thickness t of that particular layer. When etching the very top layer, at etch depths shown to induce uncharacteristically large effective propagation index contrasts and losses, the mode is no longer quasi-Gaussian within the core. (c) Estimated best mirror reflectivities of the Bragg gratings formed by etching the three different cladding layers obtained using MSE with plane wave incidence. The dash-dot horizontal lines mark the maximum reflectivity for grating in a particular layer. (d) Estimated reflectivity spectrum of a 10000 period Bragg mirror created by periodically etching the anti-resonant layer beneath the core. The etch depth is 70% of this layer, which creates an effective propagation index contrast of 5 × 10−4 with a 8% increase in loss.
Fig. 4 (a) Schematic showing how the dielectric metasurface mirror would be integrated with the hollow-core ARROW waveguide. (b) Cooperativity of hollow-core ARROW (Amode = 18µm2) cavity formed with two dielectric metasurface mirrors for various waveguide lengths and mirror reflectivities.
(8) g = μ ℏ ℏ ω 2 ϵ M V m o d e .

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